Significance H. pylori is a cause of peptic ulcer disease and gastric cancer. Only primates are naturally infected with H. pylori, and so the rhesus monkey model offers the opportunity to study the determinants of infection in a relevant animal model. Objectives These experiments are designed to (1) identify a pathogenic type strain of human-derived H. pylori that will infect rhesus monkeys; (2) isolate specific pathogen (Helicobacter free rhesus monkeys; and (3) study their response to experimental H. pylori infection. Results We screened 30 unique strains of human H. pylori for the presence of genotypic characteristics that are associated with virulence and that can be manipulated genetically. An initial group of 3 strains was selected for the first inoculation. Twenty-four nursery-raised rhesus monkeys were examined at 6 months of age by serology, endoscopy with biopsy, and urea breath test. All animals were negative for H. pylori by all methods. Three of these monkeys were orogastrically inoculated with a mixture of the 3 strains every other day for 3 days. At 2 weeks, 4 weeks, and 8 weeks post inoculation, the 3 monkeys underwent endoscopy with culture of gastric biopsies. All 3 animals were infected. Genotypic analysis of the recovered strains showed that 1 of the 3 predominated in each of the 3 animals, suggesting that it is best adapted to the rhesus monkey. Future Directions Additional animals will be inoculated with the H. pylori strain which best colonizes, and the immunologic and physiologic response to infection will be studied. KEY WORDS peptic ulcer disease, gastritis, gastric cancer FUNDING NIH Grant AI42081